The invention relates to antagonists of the neuropeptide neurokinin-1 (NK1 or NK-1) receptor.
Tachykinins are peptide ligands for neurokinin receptors. Neurokinin receptors, such as NK1, NK2 and NK3, are involved in a variety of biological processes. They can be found in a mammal's nervous and circulatory systems, as well as in peripheral tissues. Consequently, the modulation of these types of receptors have been studied to potentially treat or prevent various mammalian disease states. For instance, NK1 receptors have been reported to be involved in microvascular leakage and mucus secretion. Representative types of neurokinin receptor antagonists and the disorders that can be treated with them include, for example, sleep, pain, migraine, emesis, nociception and inflammation, see, for example, U.S. Pat. Nos. 6,329,401, 5,760,018, 5,620,989, WO 95/19344, WO 94/13639, and WO 94/10165. Cyclobutyl heterocyclic compounds can be found in: WO 99/52848, WO 99/21824 and WO 98/57940.
It would be beneficial to provide a NK, antagonist that is potent, selective, and possesses beneficial therapeutic and pharmacological properties, and good metabolic stability. It would further be beneficial to provide a NK1 antagonist that is effective for treating a variety of physiological disorders, symptoms and diseases, while minimizing side effects. This invention provides such NK1 antagonists.